Substantal progress has been made in our proposed studies. After a detailed examination of 3H-acetylcholine release from synaptosomal preparations, we concluded that the sodium-dependent, high affinity chloine uptake system and its normal function is critical for the formation of releasable acetylcholine. Causing changes in the transport system results in parallel changes in acetylcholine release. Thus, the choline transport system is critical for the normal functioning of a cholinergic nerve terminal. The choline transport system has been shown to be chloride dependent. This chloride dependence was surprising in that other sodium-dependent systems had not been reported to be chloride dependent. A thorough study in our laboratory has shown that all sodium-dependent, synaptosomal transport systems exhibit a chloride dependence. This finding, while difficult to interpret at this point in time, has important implications for the molecular mechanisms of sodium-dependent transport in synaptosomal fractions and brain tissue. Important psychoactive drugs include reserpine and the neuroleptics. Using radiolabeled drugs, we were able to map the brain for the specific receptor sites which bind these drugs. These are important basic studies pointing out sites of action of the psychoactive drugs and further studies in this area are ongoing in our laboratory.